CN106619491A - Drug sustained-release hydrogel and preparation method thereof - Google Patents
Drug sustained-release hydrogel and preparation method thereof Download PDFInfo
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- CN106619491A CN106619491A CN201710059197.XA CN201710059197A CN106619491A CN 106619491 A CN106619491 A CN 106619491A CN 201710059197 A CN201710059197 A CN 201710059197A CN 106619491 A CN106619491 A CN 106619491A
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- hydrogel
- slow release
- medicament slow
- release hydrogel
- tartaric acid
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- 239000003814 drug Substances 0.000 title claims abstract description 73
- 239000000017 hydrogel Substances 0.000 title claims abstract description 64
- 229940079593 drug Drugs 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000013268 sustained release Methods 0.000 title abstract description 6
- 239000012730 sustained-release form Substances 0.000 title abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 26
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 26
- 235000002906 tartaric acid Nutrition 0.000 claims description 26
- 239000011975 tartaric acid Substances 0.000 claims description 26
- 239000000178 monomer Substances 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 238000004806 packaging method and process Methods 0.000 claims description 17
- 235000011187 glycerol Nutrition 0.000 claims description 13
- 230000000149 penetrating effect Effects 0.000 claims description 13
- UTUUIUQHGDRVPU-UHFFFAOYSA-K aluminum;2-aminoacetate;dihydroxide;hydrate Chemical group O.[OH-].[OH-].[Al+3].NCC([O-])=O UTUUIUQHGDRVPU-UHFFFAOYSA-K 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 11
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical group CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 claims description 9
- 239000011347 resin Substances 0.000 claims description 9
- 229920005989 resin Polymers 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000012467 final product Substances 0.000 claims description 8
- 230000005251 gamma ray Effects 0.000 claims description 6
- 229960000905 indomethacin Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical group CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 4
- 238000000748 compression moulding Methods 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims 3
- 239000007864 aqueous solution Substances 0.000 claims 1
- -1 polyethylene pyrrole Pyrrolidone Polymers 0.000 claims 1
- 150000003462 sulfoxides Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 5
- 239000011159 matrix material Substances 0.000 abstract description 3
- 238000002156 mixing Methods 0.000 abstract description 2
- 238000006116 polymerization reaction Methods 0.000 abstract description 2
- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 abstract 2
- 239000004925 Acrylic resin Substances 0.000 abstract 2
- YADMSCZEQAZFKU-UHFFFAOYSA-N C(CC)S(=O)(=O)OCCCCCCCCCCCCCC.[Na].C1(\C=C/C(=O)O1)=O Chemical compound C(CC)S(=O)(=O)OCCCCCCCCCCCCCC.[Na].C1(\C=C/C(=O)O1)=O YADMSCZEQAZFKU-UHFFFAOYSA-N 0.000 abstract 2
- 239000003961 penetration enhancing agent Substances 0.000 abstract 2
- 229940047670 sodium acrylate Drugs 0.000 abstract 2
- 230000005855 radiation Effects 0.000 abstract 1
- 238000004132 cross linking Methods 0.000 description 5
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000007720 emulsion polymerization reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MQVMJSWYKLYFIG-UHFFFAOYSA-N propane-1-sulfonic acid;sodium Chemical compound [Na].CCCS(O)(=O)=O MQVMJSWYKLYFIG-UHFFFAOYSA-N 0.000 description 1
- 229920013730 reactive polymer Polymers 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F265/00—Macromolecular compounds obtained by polymerising monomers on to polymers of unsaturated monocarboxylic acids or derivatives thereof as defined in group C08F20/00
- C08F265/02—Macromolecular compounds obtained by polymerising monomers on to polymers of unsaturated monocarboxylic acids or derivatives thereof as defined in group C08F20/00 on to polymers of acids, salts or anhydrides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
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- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses drug sustained-release hydrogel, prepared from the following raw materials by weight percent: 0.1-1% of pharmaceutical molecules, 1-5% of a penetration enhancer, 0.2-2% of maleic anhydride sodium tetradecyl propane sulfonate, 6-45% of a solvent, 1-15% of sodium acrylate resin, 0.01-1% of a crosslinking agent, 1-15% of a tackifier, 0.01-0.5% of a catalyst and the balance of water. The invention also discloses a preparation method of the drug sustained-release hydrogel; the method comprises the steps of firstly, mixing the maleic anhydride sodium tetradecyl propane sulfonate with the pharmaceutical molecules, the solvent and the penetration enhancer to generate a monomer-encapsulated drug with surface activity; then, carrying out radiation polymerization on the monomer-encapsulated drug in hydrogel matrix formed by a water solution of the sodium acrylate resin, the crosslinking agent, the tackifier and the catalyst to obtain the drug sustained-release hydrogel product. The drug sustained-release hydrogel is good in slow-release effect, and the drug release stability is improved.
Description
Technical field
The present invention relates to technical field of macromolecules and medicament slow release type technical field, and in particular to be a kind of medicament slow release
Hydrogel and preparation method thereof.
Background technology
Hydrogel is cross-linked polymer of the class with high molecular weight water soluble polymer as matrix scaffold material, with drugloading rate
Greatly, moisture retention is strong, good with the compatibility of skin, and the features such as ageing-resistant, therefore hydrogel can be widely used in tissue repair, artificial
The numerous areas such as organ, medicament slow release and sensor.Being commonly used for the hydrogel plaster of slow releasing carrier of medication can repeatedly take off patch, at any time
Terminate administration；And ensureing dosage accurately, blood concentration is balanced without peak valley phenomenon, can reduce toxic and side effect；In the industrial production without
Organic solvent pollutes, and meets environmental requirement, so as to become one of the hot topic of contemporary Pharmaceutical study.
The drug release process of hydrogel is a dynamics and thermodynamic (al) recombination process, in order to allow the release of hydrogel
Effect is more stable, is usually added into powder to extend the diffusion admittance of product, the process of stable insoluble drug release, such as Japanese pharmacy
The hydrogel medicament for selling just has regulation to add kaolin to be used to stablize the process of insoluble drug release.But, existing hydrogel is still
There are problems that slow release effect it is poor, so that active ingredient can not play due drug effect, therefore, the medicine of hydrogel
The stability problem of release still has the space of further discussion.
The content of the invention
It is an object of the invention to provide a kind of medicament slow release hydrogel and preparation method thereof, the hydrogel sustained release effect of preparation
Really good, the stability of insoluble drug release increases.
In order to reach above-mentioned purpose, the solution of the present invention is：
A kind of medicament slow release hydrogel, including the raw material of following percentage by weight：
The penetrating agent is azone or dimethyl sulfoxide, and the crosslinking agent is Dihydroxyaluminium Aminoacetate, and the tackifier are poly- second
Alkene pyrrolidone, the catalyst is tartaric acid.
The drug molecule is Indomethacin or brufen.
The PAA resin is commercially available by Japanese Showa company.
The solvent is the mixture of ethanol and glycerine, and the weight percent consumption of the ethanol is 1～5%, described third
The weight percent consumption of triol is 5～40%.
The preparation method of the medicament slow release hydrogel, comprises the following steps：
(1) by 0.2～2% maleic anhydride tetradecyl alchohol base propanesulfonate, 6～45% solvent, 1～5% penetrating agent
And 0.1～1% drug molecule is well mixed, monomer packaging medicine solution is formed；
(2) aqueous tartaric acid solution is prepared into by 0.01～0.5% catalyst tartaric acid is soluble in water；
(3) 1～15% PAA tree is sequentially added in the monomer packaging medicine solution obtained to step (1)
The winestone that fat, 0.01～1% crosslinking agent Dihydroxyaluminium Aminoacetate, 1～15% tackifier polyvinylpyrrolidone and step (2) are obtained
Aqueous acid, is well mixed, and obtains the hydrogel predecessor of thick shape；
(4) by the hydrogel predecessor compression molding,60Take out after irradiation under Co gamma-rays, it is described60Co gamma-rays
Irradiation be 0.5-8kGy, obtain final product the medicament slow release hydrogel product；The consumption summation of each component is in step (1)～(3)
100%.
In step (1), the solvent is the mixture of ethanol and glycerine, the weight percent consumption of the ethanol is 1～
5%, the weight percent consumption of the glycerine is 5～40%.
Maleic anhydride tetradecyl alchohol base propanesulfonate is the reactive polymer emulsified monomer in classical emulsifier-free emulsion polymerization
【Acta Polymerica,1998,29(12):4508-4515】, with good emulsifying capacity, in technical scheme
In, as self-emulsifying monomer, first with the blending of drug molecule, solvent and penetrating agent, generation has the monomer parcel of surface-active
After medicine, by the monomer packaging medicine by PAA resin, crosslinking agent Dihydroxyaluminium Aminoacetate, tackifier polyvinylpyrrolidone and
Irradiation polymerization is carried out in the hydrogel matrix that aqueous tartaric acid solution is constituted, by irradiation so that maleic anhydride tetradecyl alchohol base propane sulfonic acid
Sodium is cross-linked to form micella particle, so as to obtain the slow releasing pharmaceutical hydrogel of stable micella particle parcel, thus improves medicine and releases
The stability put.
Description of the drawings
Fig. 1 is that the medicament slow release hydrogel (A) prepared in the embodiment of the present invention one pastes (B) with commercially available hydrogel bar cloth
Slow release effect comparison diagram.
Specific embodiment
In order to technical scheme is explained further, the present invention is explained in detail below by specific embodiment
State.
A kind of medicament slow release hydrogel, including the raw material of following percentage by weight：
The penetrating agent is azone or dimethyl sulfoxide, and the crosslinking agent is Dihydroxyaluminium Aminoacetate, and the tackifier are poly- second
Alkene pyrrolidone, the catalyst is tartaric acid.
The drug molecule is Indomethacin or brufen.
The PAA resin is commercially available by Japanese Showa company.
The solvent is the mixture of ethanol and glycerine, and the weight percent consumption of the ethanol is 1～5%, described third
The weight percent consumption of triol is 5～40%.
A kind of preparation method of medicament slow release hydrogel, comprises the following steps：
(1) by 0.2～2% maleic anhydride tetradecyl alchohol base propanesulfonate, 6～45% solvent, 1～5% penetrating agent
And 0.1～1% drug molecule is well mixed, monomer packaging medicine solution is formed；
(2) aqueous tartaric acid solution is prepared into by 0.01～0.5% catalyst tartaric acid is soluble in water；
(3) 1～15% PAA tree is sequentially added in the monomer packaging medicine solution obtained to step (1)
The winestone that fat, 0.01～1% crosslinking agent Dihydroxyaluminium Aminoacetate, 1～15% tackifier polyvinylpyrrolidone and step (2) are obtained
Aqueous acid, is well mixed, and obtains the hydrogel predecessor of thick shape；
(4) by the hydrogel predecessor compression molding,60Take out after irradiation under Co gamma-rays, it is described60Co gamma-rays
Irradiation be 0.5-8kGy, obtain final product the medicament slow release hydrogel product；The consumption summation of each component is in step (1)～(3)
100%.
Embodiment one
The preparation method of the medicament slow release hydrogel, comprises the following steps：
(1) according to formula rate, by 0.5g maleic anhydride tetradecyl alchohol base propanesulfonates, 3g ethanol, 15g glycerine, 0.35g
Indomethacin and 2g penetrating agent azones are well mixed, and form monomer packaging medicine solution；
(2) 0.1g catalyst tartaric acid is dissolved in 64.03g water and is prepared into aqueous tartaric acid solution；
(3) 10g PAA resins, 0.02g crosslinkings are sequentially added in the monomer packaging medicine solution obtained to step (1)
The aqueous tartaric acid solution that agent Dihydroxyaluminium Aminoacetate, 5g tackifier polyvinylpyrrolidone and step (2) are obtained, is well mixed, and obtains thick
The hydrogel predecessor of shape；
(4) hydrogel predecessor is molded into slabbing,60Take out after irradiation under Co gamma-rays,60The gamma-ray irradiation of Co
Measure as 4kGy, obtain final product the medicament slow release hydrogel product.
In order to preferably prove the slow release effect of the medicament slow release hydrogel, by the medicament slow release hydrogel (A) with it is commercially available
Hydrogel bar cloth patch (B) is contrasted, and the content of both drug molecules is identical, as a result as shown in figure 1, when wherein x-axis is
Between (h), y-axis for release percentage (%).As a result show：The slow release effect and stability of the medicament slow release hydrogel product all compared with
It is good.
Embodiment two
The preparation method of the medicament slow release hydrogel, comprises the following steps：
(1) according to formula rate, by 0.8g maleic anhydride tetradecyl alchohol base propanesulfonates, 3g ethanol, 20g glycerine, 0.5g
Indomethacin and 2.5g penetrating agent azones are well mixed, and form monomer packaging medicine solution；
(2) 0.1g catalyst tartaric acid is dissolved in 55.08g water and is prepared into aqueous tartaric acid solution；
(3) 10g PAA resins, 0.02g crosslinkings are sequentially added in the monomer packaging medicine solution obtained to step (1)
The aqueous tartaric acid solution that agent Dihydroxyaluminium Aminoacetate, 8g tackifier polyvinylpyrrolidone and step (2) are obtained, is well mixed, and obtains thick
The hydrogel predecessor of shape；
(4) hydrogel predecessor is molded into slabbing,60Take out after irradiation under Co gamma-rays,60The gamma-ray irradiation of Co
Measure as 0.5kGy, obtain final product the medicament slow release hydrogel product.
Embodiment three
The preparation method of the medicament slow release hydrogel, comprises the following steps：
(1) according to formula rate, by 2g maleic anhydride tetradecyl alchohol base propanesulfonates, 3g ethanol, 10g glycerine, 0.5g Yin
The pungent and 3g penetrating agent dimethyl sulfoxides of diindyl U.S. are well mixed, and form monomer packaging medicine solution；
(2) 0.1g catalyst tartaric acid is dissolved in 54.35g water and is prepared into aqueous tartaric acid solution；
(3) 15g PAA resins, 0.05g crosslinkings are sequentially added in the monomer packaging medicine solution obtained to step (1)
The aqueous tartaric acid solution that agent Dihydroxyaluminium Aminoacetate, 12g tackifier polyvinylpyrrolidone and step (2) are obtained, is well mixed, and obtains thick
The hydrogel predecessor of shape；
(4) hydrogel predecessor is molded into slabbing,60Take out after irradiation under Co gamma-rays,60The gamma-ray irradiation of Co
Measure as 2kGy, obtain final product the medicament slow release hydrogel product.
Example IV
The preparation method of the medicament slow release hydrogel, comprises the following steps：
(1) according to formula rate, by 1.5g maleic anhydride tetradecyl alchohol base propanesulfonates, 5g ethanol, 20g glycerine, 0.5g
Brufen and 2g penetrating agent azones are well mixed, and form monomer packaging medicine solution；
(2) 0.1g catalyst tartaric acid is dissolved in 50.7g water and is prepared into aqueous tartaric acid solution；
(3) 15g PAA resins, 0.2g crosslinkings are sequentially added in the monomer packaging medicine solution obtained to step (1)
The aqueous tartaric acid solution that agent Dihydroxyaluminium Aminoacetate, 5g tackifier polyvinylpyrrolidone and step (2) are obtained, is well mixed, and obtains thick
The hydrogel predecessor of shape；
(4) hydrogel predecessor is molded into slabbing,60Take out after irradiation under Co gamma-rays,60The gamma-ray irradiation of Co
Measure as 6kGy, obtain final product the medicament slow release hydrogel product.
Embodiment five
The preparation method of the medicament slow release hydrogel, comprises the following steps：
(1) according to formula rate, by 1g maleic anhydride tetradecyl alchohol base propanesulfonates, 3g ethanol, 15g glycerine, 0.5g Yin
The pungent and 4g penetrating agent dimethyl sulfoxides of diindyl U.S. are well mixed, and form monomer packaging medicine solution；
(2) 0.4g catalyst tartaric acid is dissolved in 54.3g water and is prepared into aqueous tartaric acid solution；
(3) 12g PAA resins, 0.8g crosslinkings are sequentially added in the monomer packaging medicine solution obtained to step (1)
The aqueous tartaric acid solution that agent Dihydroxyaluminium Aminoacetate, 9g tackifier polyvinylpyrrolidone and step (2) are obtained, is well mixed, and obtains thick
The hydrogel predecessor of shape；
(4) hydrogel predecessor is molded into slabbing,60Take out after irradiation under Co gamma-rays,60The gamma-ray irradiation of Co
Measure as 8kGy, obtain final product the medicament slow release hydrogel product.
The product form and style of above-described embodiment and schema and the non-limiting present invention, any art it is common
Appropriate change or modification that technical staff is done to it, all should be regarded as the patent category without departing from the present invention.
Claims (5)
1. a kind of medicament slow release hydrogel, it is characterised in that：Including the raw material of following percentage by weight：
The penetrating agent is azone or dimethyl sulfoxide, and the crosslinking agent is Dihydroxyaluminium Aminoacetate, and the tackifier are polyethylene pyrrole
Pyrrolidone, the catalyst is tartaric acid.
2. a kind of medicament slow release hydrogel according to claim 1, it is characterised in that：The drug molecule is Indomethacin
Or brufen.
3. a kind of medicament slow release hydrogel according to claim 1, it is characterised in that：The solvent is ethanol and glycerine
Mixture, the weight percent consumption of the ethanol is 1～5%, and the weight percent consumption of the glycerine is 5～40%.
4. a kind of preparation method of medicament slow release hydrogel as claimed in claim 1 is prepared, it is characterised in that：Including following step
Suddenly：
(1) by 0.2～2% maleic anhydride tetradecyl alchohol base propanesulfonate, 6～45% solvent, 1～5% penetrating agent and
0.1～1% drug molecule is well mixed, and forms monomer packaging medicine solution, and the penetrating agent is azone or diformazan
Sulfoxide；
(2) aqueous tartaric acid solution is prepared into by 0.01～0.5% catalyst tartaric acid is soluble in water；
(3) sequentially add in the monomer packaging medicine solution obtained to step (1) 1～15% PAA resin,
The tartaric acid that 0.01～1% crosslinking agent Dihydroxyaluminium Aminoacetate, 1～15% tackifier polyvinylpyrrolidone and step (2) are obtained
The aqueous solution, is well mixed, and obtains the hydrogel predecessor of thick shape；
(4) by the hydrogel predecessor compression molding,60Take out after irradiation under Co gamma-rays, it is described60The gamma-ray irradiation of Co
Measure as 0.5-8kGy, obtain final product the medicament slow release hydrogel product；The consumption summation of each component is 100% in step (1)～(3).
5. the preparation method of a kind of medicament slow release hydrogel according to claim 4, it is characterised in that：In step (1), institute
The mixture that solvent is ethanol and glycerine is stated, the weight percent consumption of the ethanol is 1～5%, the weight of the glycerine
Percentage amount is 5～40%.
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